Validation of the motivated strategies for learning questionnaire and instructional materials motivation survey.

PURPOSE: To validate the Motivated Strategies for Learning Questionnaire (MSLQ), which measures learner motivations; and the Instructional Materials Motivation Survey (IMMS), which measures the motivational properties of educational activities. METHODS: Participants (333 pharmacists, physicians, and advanced practice providers) completed the MSLQ, IMMS, Congruence-Personalization Questionnaire (CPQ), and a knowledge test immediately following an online learning module (April 2021). We randomly divided data for split-sample analysis using confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and the multitrait-multimethod matrix. RESULTS: Cronbach alpha was ≥0.70 for most domains. CFA using sample 1 demonstrated suboptimal fit for both instruments, including 3 negatively-worded IMMS items with particularly low loadings. Revised IMMS (RIMMS) scores (which omit negatively-worded items) demonstrated better fit. Guided by EFA, we identified a novel 3-domain, 11-item 'MSLQ-Short Form-Revised' (MSLQ-SFR, with domains: Interest, Self-efficacy, and Attribution) and the 4-domain, 12-item RIMMS as the best models. CFA using sample 2 confirmed good fit. Correlations among MSLQ-SFR, RIMMS, and CPQ scores aligned with predictions; correlations with knowledge scores were small. CONCLUSIONS: Original MSLQ and IMMS scores show poor model fit, with negatively-worded items notably divergent. Revised, shorter models-the MSLQ-SFR and RIMMS-show satisfactory model fit (internal structure) and relations with other variables.

Ketamine for Primary Analgosedation in Critically Ill Surgery and Trauma Patients Requiring Mechanical Ventilation.

OBJECTIVES: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. DESIGN: Retrospective cohort study. SETTING: Academic medical center in Minnesota. PATIENTS: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. INTERVENTIONS: None. MEASUREMENTS: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. MAIN RESULTS: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. CONCLUSIONS: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.

Personalisation and embodiment in e-Learning for health professionals: A randomised controlled trial.

PURPOSE: Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e-Learning. The authors hypothesised that an e-Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. METHODS: The authors conducted a randomised trial comparing two versions of a 30-minute multimedia e-Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human-like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. RESULTS: There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post-module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI -0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e-Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats (p > 0.05). CONCLUSION: Application of P/E principles to an e-Learning module led to greater perceived P/E and motivational features but did not influence knowledge.

Measuring Personalization, Embodiment, and Congruence in Online Learning: A Validation Study.

PURPOSE: Instructional designs promoting personalization (conversational style and visible author), embodiment (human-like mannerisms and presence), and social and cognitive congruence have been shown to enhance learning. However, measurements of these instructional design features are lacking. The authors sought to develop and validate an instrument to measure personalization, embodiment, and congruence in an online course, collecting evidence of content, internal structure, and relationships with other variables. METHOD: Through literature review, expert review, and pilot testing, the authors developed a 15-item, 5-domain instrument. Participants completed this instrument along with assessments of motivation (Instructional Materials Motivation Survey and Motivated Strategies for Learning Questionnaire), knowledge, and course satisfaction immediately after a 30-minute online multimedia learning module comprising slides with voiceover and (for some participants) short video clips, from January to April 2021. Participants included pharmacists, physicians, and advanced practice providers at academic and community hospitals. Confirmatory factor analysis (CFA) was used to examine model fit, followed by structural revisions guided by exploratory factor analysis (EFA) and tested in a new CFA using a split-sample approach. The authors evaluated associations between the revised instrument scores and motivation, knowledge, and satisfaction. RESULTS: There were 406 participants. CFA of the original 15-item instrument revealed poor model fit. EFA using 214 randomly selected participants suggested a 2-domain structure. CFA of the revised structure using the other 192 participants revealed good fit for a 9-item, 2-domain instrument: the Congruence-Personalization Questionnaire (CPQ). Linear regression confirmed positive, statistically significant associations for most hypothesized relationships (R 2 ≥ 0.12 and P < .001 for 14 of 18 associations with motivation and satisfaction). Associations with knowledge were weak and nonsignificant (R 2 ≤ 0.004, P > .23). CONCLUSIONS: Evidence of content, internal structure, and relationships with other variables support the validity of CPQ scores for measuring personalization and congruence in an online module.

Impact of a Systematic Pharmacist-Initiated Antibiotic Time-Out Intervention for Hospitalized Adults.

INTRODUCTION: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. METHODS: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. RESULTS: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). DISCUSSION: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.

Evaluation of Piperacillin-Tazobactam for Antibiotic Prophylaxis in Traumatic Grade III Open Fractures.

Background: Broad-spectrum antibiotic agents are sometimes utilized for prophylaxis of Gustilo grade III open fractures. However, this practice is not recommended by current guidelines, and it is unknown how patient outcomes are impacted. This study aimed to determine if prophylaxis with piperacillin-tazobactam (PT) results in different rates of infection versus guideline-concordant therapy (GCT). Patients and Methods: This was a single-center, retrospective cohort study of adult trauma patients with Gustilo grade III open long bone fractures admitted between January 2008 and August 2018. The primary outcome of infection (superficial or deep) at six weeks and secondary outcomes of delayed union, nonunion, Clostridioides difficile, and development of resistant organisms were abstracted from medical records. Guideline-concordant therapy was defined as a first-generation cephalosporin with or without an aminoglycoside. Univariable and multivariable analyses controlling for injury severity score (ISS) were performed. Results: One hundred twenty patients were included; 97 (81%) received PT, 23 (19%) received GCT. Common injury mechanisms were motor vehicle/motorcycle accident (57%) and falls (17%), and a majority involved a lower extremity (65%). Baseline characteristics were similar except higher median ISS in PT (14; interquartile range [IQR], 9-22) versus GCT (9; IQR, 9-14). Guideline-concordant therapy was given for a median of four (range, 2-8) days and PT for six (range, 3-11) days (p = 0.078). On univariable analysis, PT patients had more infections at six weeks (23.7% vs. 4.3%; p = 0.042), but multivariable analysis demonstrated no difference (odds ratio [OR], 5.81; 95% confidence interval [CI], 0.73-46.25; p = 0.096). Patients receiving prophylaxis with PT had a longer median length of stay at 16 days (range, 10-22) versus nine days (range, 4-16). No statistically significant differences in delayed union, non-union, Clostridioides difficile, or development of resistant organisms were observed. Conclusions: Broad-spectrum antibiotic prophylaxis with PT did not improve infection rates compared to GCT, suggesting it may not be warranted.

Ability of the Well-Being Index to identify pharmacists in distress.

BACKGROUND: Well-being and distress are important issues in the pharmacist workforce; yet, there is limited evidence evaluating the validity of practical screening tools among pharmacists. OBJECTIVES: To evaluate the ability of the Well-Being Index (WBI) to (1) identify the well-being and dimensions of distress in pharmacists, and (2) stratify pharmacists' likelihood of adverse professional consequences. METHODS: In July 2019, a national sample of pharmacists completed the Web-based version of the 9-item WBI (score range -2 to 9) and standardized instruments to assess quality of life (QOL), fatigue, burnout, concern for a recent major medication error, and intent to leave the current job. The Fisher exact test or chi-square test was used, as appropriate, to obtain the univariate odds ratio, posttest probabilities, and likelihood ratios associated with the WBI score for each outcome. RESULTS: A total of 2231 pharmacists completed the survey. The most common practice settings were community pharmacies-chain (36.7%) and independent (10.7%)-followed by hospitals or health systems (20.1%) and academia (11.7%). The mean overall WBI score was 3.3 ± 2.73 (mean ± SD). Low QOL, extreme fatigue, and burnout symptoms were present in 34.8%, 35.3%, and 59.1%, respectively, of the responders. As the WBI score increased, the odds for low QOL, fatigue, burnout, concern for a recent major medication error, and intent to leave the current position increased incrementally. The WBI score also stratified the odds of high QOL. Assuming a pretest burnout probability of 59.1% (prevalence of the overall sample), the WBI lowered the posttest probability to 2% or raised it to 98% with an area under the receiver operating characteristic curve of 0.87. CONCLUSION: The WBI may serve as a useful tool to gauge well-being and to identify pharmacists who may be experiencing important dimensions of distress and have increased risk for adverse professional consequences.

Examining the Relationship Between Vancomycin Area Under the Concentration Time Curve and Serum Trough Levels in Adults With Presumed or Documented Staphylococcal Infections.

BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing, but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using 2-level pharmacokinetic monitoring to inform changes to an institutional vancomycin dosing protocol. METHODS: This was a retrospective observational study performed in 2 acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20 mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to minimum inhibitory concentration ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected. RESULTS: Thirty-four patients were included in the study, with 2 patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%), and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± SD vancomycin Cmin was 16.6 ± 6.1 mg/L, and the mean AUC/MIC was 588 ± 156 mg/L × hour. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n = 31/34). Of the patients with a Cmin > 9 mg/L, 100% (n = 33) achieved AUC/MIC values >400 mg/L × hour and 93.9% were >500 mg/L × hour. There was a strong correlation between vancomycin Cmin and AUC24 hr (R = 0.731; P < 0.001). CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than that thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.

Confronting the Challenge of Beta-Lactam Allergies: A Quasi-Experimental Study Assessing Impact of Pharmacy-Led Interventions.

OBJECTIVE: To improve allergy history documentation and increase the use of beta-lactams when appropriate in patients with a reported beta-lactam allergy. METHODS: This pre-post study was conducted at a 167-bed tertiary care community hospital and evaluated multidisciplinary interventions on allergy documentation and antibiotic selection. Interventions included education, creation of local practice guidelines, and modified practices for pharmacists and pharmacy technicians. Inpatients with a reported beta-lactam allergy receiving at least 1 antibiotic for >24 hours were included; first admissions were assessed. Primary outcomes were documentation of reaction type and percentage of patients receiving non-beta-lactam therapy. Secondary outcomes included documentation of previously tolerated beta-lactams, modification of non-beta-lactam therapy, discharge antibiotics, and adverse reactions. RESULTS: A total of 179 patients were included, 91 preintervention and 88 postintervention. No significant differences were observed between the before versus after groups in the percentage of patients with documentation of reaction type (90.1% vs 89.8%, P = .940) or the overall percentage of patients receiving non-beta-lactams (86.8% vs 84.1%, P = .605). However, significantly more patients in the after phase had documentation of previously tolerated beta-lactams (8.8% vs 28.4%, P = .001), and among patients receiving a non-beta-lactam, a greater percentage was subsequently switched to a beta-lactam (11.4% vs 25.7%, P = .022). One allergic reaction was documented during the study, which occurred in the before phase. CONCLUSION: Multidisciplinary education and local guideline implementation led by pharmacists may improve allergy documentation and antibiotic selection in patients with reported beta-lactam allergies.

Road Map for Research Training in the Residency Learning Experience.

The American Society of Health-System Pharmacists residency accreditation standards require all postgraduate residency training programs to teach and evaluate a resident's ability to advance practice through project development and presentation, underscoring the importance of conducting research in today's professional climate. Although many residents express strong interest in research participation and contributing to the medical literature, many obstacles to publication have been identified. We aim to illustrate a deliberate approach to teaching this material and structuring the longitudinal experience in a way that maximizes resources to overcome these barriers. Such efforts should aid residents, advisors, and program directors in establishing curriculum which leads to successful completion and publication of pharmacy resident's research projects.

Inadequate Source Control and Inappropriate Antibiotics are Key Determinants of Mortality in Patients with Intra-Abdominal Sepsis and Associated Bacteremia.

BACKGROUND: Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. METHODS: This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. RESULTS: Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. CONCLUSIONS: Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: a before-after study.

INTRODUCTION: Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared with benzodiazepines; however, further study and validation are needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. METHODS: We conducted a before-after study including adult surgical and medical intensive care unit (ICU) patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between 1 April 2011 and 31 August 31 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach, and staff education was provided. The after phase included consecutive eligible patients between 1 May 2012 and 31 October 2012. RESULTS: A total of 199 patients were included, with 97 patients in the before phase and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% versus 27%, P <0.0001) or at any point during the ICU stay (76% versus 48%, P <0.0001) was significantly reduced in the after phase. Dexmedetomidine use as initial sedation (2% versus 39%, P <0.0001) or at any point during the ICU stay (39% versus 82%, P <0.0001) significantly increased. Both the prevalence (81% versus 93%, P =0.013) and median percentage of days with delirium (55% (interquartile range (IQR), 18 to 83) versus 71% (IQR, 45 to 100), P =0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR, 59 to 192) hours versus 74.5 (IQR, 42 to 148) hours, P =0.029), and significantly fewer patients required tracheostomy (20% versus 9%, P =0.040). The median ICU length of stay was 8 (IQR, 4 to 12) days in the before phase and 6 (IQR, 3 to 11) days in the after phase (P =0.252). CONCLUSIONS: Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and the requirement for tracheostomy, despite increases in the prevalence and duration of ICU delirium.

The presence of hypothermia within 24 hours of sepsis diagnosis predicts persistent lymphopenia.

OBJECTIVE: To determine whether hypothermia within 24 hours of sepsis diagnosis is associated with development of persistent lymphopenia, a feature of sepsis-induced immunosuppression. DESIGN: Retrospective cohort study. SETTING: A 1,200-bed university-affiliated tertiary care hospital. PATIENTS: Adult patients diagnosed with bacteremia and sepsis within 5 days of hospital admission between January 1, 2010, and July 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Leukocyte counts were recorded during the first 4 days following sepsis diagnosis. Persistent lymphopenia was defined as an absolute lymphocyte count less than 1.2 cells/µL×10(3) present on the fourth day after diagnosis. Of the 445 patients with sepsis included, hypothermia developed in 64 patients (14.4%) (defined as a body temperature<36.0°C) within 24 hours of sepsis diagnosis. Hypothermia was a significant independent predictor of persistent lymphopenia (adjusted odds ratio, 2.70 [95% CI, 1.10, 6.60]; p=0.03) after accounting for age, disease severity, comorbidities, source of bacteremia, and type of organism. Compared with the nonhypothermic patients, hypothermic patients had higher 28-day (50.0% vs 24.9%, p<0.001) and 1-year mortality (60.9% vs 47.0%, p=0.001). CONCLUSIONS: Hypothermia is associated with higher mortality and an increased risk of persistent lymphopenia in patients with sepsis, and it may be an early clinical predictor of sepsis-induced immunosuppression.

Persistent lymphopenia after diagnosis of sepsis predicts mortality.

OBJECTIVE: The objective of this study was to determine whether persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts mortality. METHODS: This was a single-center, retrospective cohort study of 335 adult patients with bacteremia and sepsis admitted to a large university-affiliated tertiary care hospital between January 1, 2010, and July 31, 2012. All complete blood cell count profiles during the first 4 days following the diagnosis of sepsis were recorded. The primary outcome was 28-day mortality. Secondary outcomes included development of secondary infections, 1-year mortality, and hospital and intensive care unit lengths of stay. RESULTS: Seventy-six patients (22.7%) died within 28 days. Lymphopenia was present in 28-day survivors (median, 0.7 × 10 cells/µL; interquartile range [IQR], 0.4-1.1 × 10 cells/µL) and nonsurvivors (median, 0.6 × 10 cells/µL; IQR, 0.4-1.1 × 10 cells/µL) at the onset of sepsis and was not significantly different between the groups (P = 0.35). By day 4, the median absolute lymphocyte count was significantly higher in survivors compared with nonsurvivors (1.1 × 10 cells/µL [IQR, 0.7-1.5 × 10 cells/µL] vs. 0.7 × 10 cells/µL [IQR, 0.5-1.0 × 10 cells/µL]; P < 0.0001). Using logistic regression to account for potentially confounding factors (including age, Acute Physiology and Chronic Health Evaluation II score, comorbidities, surgical procedure during the study period, and time until appropriate antibiotic administration), day 4 absolute lymphocyte count was found to be independently associated with 28-day survival (adjusted odds ratio, 0.68 [95% confidence interval, 0.51-0.91]) and 1-year survival (adjusted odds ratio, 0.74 [95% confidence interval, 0.59-0.93]). Severe persistent lymphopenia (defined as an absolute lymphocyte count of 0.6 × 10 cells/µL or less on the fourth day after sepsis diagnosis) was associated with increased development of secondary infections (P = 0.04). CONCLUSIONS: Persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts early and late mortality and may serve as a biomarker for sepsis-induced immunosuppression.

Current strategies for the treatment of complicated intraabdominal infections.

INTRODUCTION: Complicated intraabdominal infections (cIAIs) are a common cause of infection-related morbidity and mortality in hospitalized patients and present many challenges unique from other serious infections. cIAIs are generally polymicrobial in nature; however, controversy exists around the pathogenicity of some of the frequently identified microorganisms. Increasing antibiotic resistance among commonly isolated bacteria poses further challenges for clinicians managing patients with cIAIs. AREAS COVERED: This article highlights the microbiology and recent trends in antibiotic resistance most relevant to cIAIs, provides recommendations for treatment using currently available antimicrobials and introduces antibiotics in development with potential roles in managing cIAIs. EXPERT OPINION: Successful treatment of cIAI requires a combination of timely source control and thorough assessment of patient characteristics to guide selection of an appropriate empiric antimicrobial regimen. Specific considerations that should be made when choosing antibiotics include the origin of infection, presence of risk factors for potentially resistant pathogens and severity of disease. While it is encouraging that agents in development may prove helpful in the treatment of cIAIs with resistant pathogens, further identification of novel antibiotics is needed to address this growing concern. In addition, adherence to the principles of antimicrobial stewardship is needed if current antimicrobial resources are to be preserved for the treatment of cIAIs.

Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study.

BACKGROUND: ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Heparin or 0.9% sodium chloride to maintain central venous catheter patency: a randomized trial.

OBJECTIVE: To compare heparin (3 mL, 10 units/mL) and 0.9% sodium chloride (NaCl, 10 mL) flush solutions with respect to central venous catheter lumen patency. DESIGN: Single-center, randomized, open label trial. SETTING: Medical intensive care unit and Surgical/Burn/Trauma intensive care unit at Barnes-Jewish Hospital, St. Louis, MO. PATIENTS: Three hundred forty-one patients with multilumen central venous catheters. Patients with at least one lumen with a minimum of two flushes were included in the analysis. INTERVENTIONS: Patients were randomly assigned within 12 hrs of central venous catheter insertion to receive either heparin or 0.9% sodium chloride flush. MEASUREMENTS AND MAIN RESULTS: The primary outcome was lumen nonpatency. Secondary outcomes included the rates of loss of blood return, inability to infuse or flush through the lumen (flush failure), heparin-induced thrombocytopenia, and catheter-related blood stream infection. Assessment for patency was performed every 8 hrs in lumens without continuous infusions for the duration of catheter placement or discharge from intensive care unit. Three hundred twenty-six central venous catheters were studied yielding 709 lumens for analysis. The nonpatency rate was 3.8% in the heparin group (n = 314) and 6.3% in the 0.9% sodium chloride group (n = 395) (relative risk 1.66, 95% confidence interval 0.86-3.22, p = .136). The Kaplan-Meier analysis for time to first patency loss was not significantly different (log rank = 0.093) between groups. The rates of loss of blood return and flush failure were similar between the heparin and 0.9% sodium chloride groups. Pressure-injectable central venous catheters had significantly greater rates of nonpatency (10.6% vs. 4.3%, p = .001) and loss of blood return (37.0% vs. 18.8%, p <.001) compared to nonpressure-injectable catheters. The frequencies of heparin-induced thrombocytopenia and catheter-related blood stream infection were similar between groups. CONCLUSION: 0.9% sodium chloride and heparin flushing solutions have similar rates of lumen nonpatency. Given potential safety concerns with the use of heparin, 0.9% sodium chloride may be the preferred flushing solution for short-term use central venous catheter maintenance.

A comparison of ventilator-associated pneumonia rates as identified according to the National Healthcare Safety Network and American College of Chest Physicians criteria.

OBJECTIVE: The objective of this study was to compare the observed rates of ventilator-associated pneumonia when using the National Healthcare Safety Network vs. the American College of Chest Physicians criteria. DESIGN: Prospective, observational cohort study. SETTING: A 1250-bed academic tertiary care medical center. PATIENTS: Adult medical and surgical intensive care unit patients requiring mechanical ventilation for >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively and independently screened for ventilator-associated pneumonia from January 2009 to January 2010 using the National Healthcare Safety Network and American College of Chest Physicians criteria. All American College of Chest Physicians classifications, including the corresponding radiographs and laboratory data, were prospectively reviewed by one of the investigators (JD) and confirmed by a second investigator (MHK). All National Healthcare Safety Network classifications were administratively determined using the hospital's infection prevention surveillance system. Over 1 yr, 2060 patients met the inclusion criteria. Of these, 83 patients (4%) had ventilator-associated pneumonia according to the American College of Chest Physicians criteria as compared with 12 patients (0.6%) using the National Healthcare Safety Network criteria. The corresponding rates of ventilator-associated pneumonia were 8.5 vs. 1.2 cases per 1,000 ventilator days, respectively. Agreement of the two sets of criteria was marginal (κ statistic, 0.26). Cultures were positive in 88% of ventilator-associated pneumonias in the American College of Chest Physicians group as compared to 92% in the National Healthcare Safety Network group. CONCLUSIONS: There is poor agreement between clinical and administrative surveillance methods for the diagnosis of ventilator-associated pneumonia. Although there may be some benefit to using more stringent criteria for surveillance of ventilator-associated pneumonia, use of the administratively applied National Healthcare Safety Network criteria may significantly underestimate the scope of the clinical problem.

Advances in the management of sepsis and the understanding of key immunologic defects.

Anesthesiologists are increasingly confronting the difficult problem of caring for patients with sepsis in the operating room and in the intensive care unit. Sepsis occurs in more than 750,000 patients in the United States annually and is responsible for more than 210,000 deaths. Approximately 40% of all intensive care unit patients have sepsis on admission to the intensive care unit or experience sepsis during their stay in the intensive care unit. There have been significant advances in the understanding of the pathophysiology of the disorder and its treatment. Although deaths attributable to sepsis remain stubbornly high, new treatment algorithms have led to a reduction in overall mortality. Thus, it is important for anesthesiologists and critical care practitioners to be aware of these new therapeutic regimens. The goal of this review is to include practical points on important advances in the treatment of sepsis and provide a vision of future immunotherapeutic approaches.